A recent study found that rats with advanced fibrosis that were administered a short-term dose of losartan-M6PHSA had reduced liver inflammation and fibrosis. Those animals treated with oral losartan alone did not experience a similar reduction in disease activity. Results of this study appear in the March issue of Hepatology, a journal published by Wiley-Blackwell on behalf of the American Association for the Study of Liver Diseases.

Liver fibrosis a consequence of liver disease was thought to be irreversible and only transplantation of the liver would offer survival to the patient. Doctors now believe that early detection of fibrosis offers potential for therapies that prevent further liver scarring and the imminent need for transplantation.

In the current study, a Spanish research team led Ramón Bataller, M.D., from the Hospital Clínic in Barcelona investigated such a treatment, losartan-M6PHSA, in rat models. Losartan is an angiotensin (AT1) receptor blocker that was linked to mannose-6-phosphate modified human serum albumin (M6PHSA), a selective drug carrier targeting hepatic stellate cells (HSC). An average of 7 losartan molecules were coupled to M6PHSA. The study verified that losartan-M6PHSA accumulates in the fibrotic liver only, and other organs such as the lungs, heart, spleen and kidneys did not display the conjugate.

In the long-term results, advanced liver fibrosis was established in male rats by chronic treatment of carbon tetrachloride (CCl4 ). Treatment by saline, losartan-M6PHSA or M6PHSA alone was administered twice a week for three weeks. "While losartan-M6PHSA was able to reduce collagen synthesis, the degree of fibrosis reduction was not significant. Further studies identifying the ideal route and drug dosage for long-term treatment are clearly required," concluded Dr. Bataller.

Hepatology is the premier publication in the field of liver disease, publishing original, peer-reviewed articles concerning all aspects of liver structure, function and disease. Each month, the distinguished Editorial Board monitors and selects only the best articles on subjects such as immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases and their complications, liver cancer, and drug metabolism. Hepatology is published on behalf of the American Association for the Study of Liver Diseases (AASLD). For more information, please visit http://www3.interscience.wiley.com/journal/106570044/home.

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